Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumor cells. In humans, the activating natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 play a major role in NK cell-mediated tumor cell lysis. NKp30 recognizes B7-H6, a member of the B7 family. Like all known B7 family members, B7-H6 includes two Ig domains with adjacent phase introns in the extracellular region. Importantly, B7-H6 is not detected in normal human tissues but is selectively expressed on a variety of human tumor cell lines, including T and B lymphomas, melanomas, and carcinomas (Brandt, et al. (2009) J. Exp. Med. 206:1495-1503). Furthermore, B7-H6 expression on tumor cells triggers NKp30-specific NK cell cytotoxicity and cytokine secretion. Thus, B7-H6 functions as a tumor-induced self-molecule that alerts innate immunity to cellular transformation via its interaction with the activating receptor NKp30 (Brandt, et al. (2009) supra).